Delayed puberty and secondary amenorrhea due to hypothalamic mechanisms in young women are common events which are thought to be reversible and without permanent health effects. However, it is a well documented clinical observation that young women deprived of estrogen are at increased risk for the development of osteoporosis. No systematic study has been performed to date on young women who have repeated episodes of prolonged hypoestrogenism at a young age to document the occurrence and development of permanent long term problems such as osteopenia. In addition, the apposition of bone during adolescence is thought to have a critical bearing on the development of osteoporosis in later life. Yet, little scientific data exists on the effects of prolonged periods of hypoestrogenism during this critical period. Recent data shows that prolonged hypoestrogenism may be related to skeletal problems seen in young adults. The present research proposal is aimed at examining whether prolonged hypoestrogenism in young women affects bone density in the same manner that is documented in postmenopausal women. The pathogenesis of hypoestrogenism and skeletal complications which occur in a unique high risk group of young adults and adolescent girls will be examined in a detailed longitudinal fashion. This group shows a high incidence of stress fractures (46%) and adolescent scoliosis (23%) as well as prolonged intervals of hypoestrogenism manifested by delayed menarche or secondary amenorrhea. Intensive serial studies of 80 cohort members and 80 controls will be performed. These studies will be analyzed to elucidate the potential interrelationships of prolonged hypoestrogenism and abnormal nutritional patterns to the pathogenesis of osteopenia and scoliosis. Further understanding of the role of hypoestrogenism in the development of stress fractures and scoliosis would radically alter attitudes towards the importance of normal sexual maturation and estrogen replacement and may lead to the formulation of more effective treatment strategies for scoliosis.